Characterization of lymphomas occurring in old mice has been carried out by studying the histopathology, karyology, cell surface antigens, intracytoplasmic immunoglobulin light and heavy chains, development of cell lines, both in vivo and in vitro. Identification of these lymphomas to be composed of B lymphocytes, mainly large and/or small follicular center cells, has been established. In addition, 4 cases of chronic lymphocytic leukemia and 2 of pre-B lymphoma have been identified. All cell lines developed in vitro (6) are of B lymphocytes as well as those studied for surface antigens of the 9 passaged in vivo. The in vitro lines have generally 41 chromosomes and the extra chromosome is being identified. Thus, as in humans, lymphomas associated with advanced age in mice are derived from clones (intracytoplasmic IG substantiates the clonal origin) of malignant B lymphocytes, most of which are in a fairly advanced stage of differentiation.